Sustained CD4+ cell count increases as a result of potent anti-HIV therapy have been credited with a steep drop in many HIV-related conditions. Indeed, the most recent guidelines for preventing opportunistic infections (OIs) reflect the growing practice of stopping preventive and maintenance therapies. While the risk of developing OIs or having them reappear still exists after therapy fails, the possibility of stopping OI therapy after achieving an improved immune response is promising for many. Unfortunately, despite success with many OIs, declines in the rate of the fungal infection candidiasis have not been observed.

What is Candidiasis?

Candidiasis is caused by the fungus Candida and while it is a relatively common condition in general, it remains the most common HIV-associated disease. Some lab studies show that protease inhibitors have a direct anti-Candida effect. Other studies suggest that the chance of developing candidiasis does not significantly decrease when using combination anti-HIV therapy. Thus, at one point or another, candidiasis continues to affect the majority of people with HIV disease who suffer from clinical declines in immune function. In people with damaged or weakened immune systems, Candida can recur and be difficult to treat.

Candidiasis can occur in the mouth, esophagus (throat), digestive tract, vagina or on the skin. The most common site of infection is in the mouth (thrush) and/or vagina (yeast infections, vaginitis). Among women, vaginal candidiasis appears as the most common symptom. Although vaginal candidiasis is slightly more common among HIV-positive women than negative women, there is no clear relationship between its occurrence and CD4+ cell count. Thus, the relationship between vaginal candidiasis and HIV infection remains unclear. Finally, esophageal candidiasis has been reported as the most common AIDS-defining OI, probably due to the decreased incidence of other OIs.

Symptoms of Candidiasis

Thrush can sometimes occur without symptoms. However, the most common symptoms of oral candidiasis include burning pain, altered taste, difficulty swallowing and/or whitish coatings or spots on the gums and tongue. Thrush is rare when CD4+ cell counts are above 500 and more common as CD4+ cell counts decrease and near 100.

Esophageal candidiasis tends to occur more frequently when CD4+ cell counts are below 100. It is usually accompanied by thrush and esophageal/throat pain.

Treatment Considerations

The range of treatments for candidiasis boil down to two kinds: local (treating at the site of the disease) or systemic (treating the disease throughout the body). Local therapies include topical creams to treat Candida infections in the skin, vaginal creams to treat vaginal candidiasis and lozenges or mouth washes to treat Candida in the mouth. Systemic therapy include pills (taken by mouth) and intravenous (in the vein) therapies. Generally speaking, local therapy will be the first choice for treating candidiasis. If the infection is aggressive, not responsive to therapy and/or shows signs of spreading throughout the body, then systemic therapy will be employed.

Systemic therapies can be used for any type of candidiasis. They must be used for esophageal candidiasis or candidiasis that has spread throughout the body. Intravenous treatment is generally the least desired option because it can have many side effects. It is left as a last resort in rare but serious, life-threatening cases that have not responded to other treatments.

The Problem of Antifungal Resistance

Candidiasis that fails to respond to treatment has been increasingly reported, especially among people who have not experienced benefit from fluconazole (Diflucan) and other azole antifungal drugs. This is partly due to the widespread, long-term use of azole drugs for treating and preventing candidiasis. Other factors associated with azole-resistance include tuberculosis (TB) exposure, treatment with anti-TB drugs, treatment with the antibiotic ciprofloxacin (Cipro) and CD4+ cell counts below 50.

Resistance to azole drugs has often required treatment with amphotericin B (Fungizone). While potent and effective, amphotericin B -- both intravenous and oral formulas -- is toxic, especially to the kidney. Newer liposomal versions of the drug, such as amphotericin B lipid complex or ABLC, have proven less toxic to the kidneys than its earlier formula.

A recent study compared the original form of the drug to the newer form in people who could not tolerate conventional amphotericin B and/or who did not respond to the drug. The study found that people were more likely to tolerate ABLC and were thus more likely to be able to take the drug until their fungal infection successfully cleared. Even among people with some underlying kidney disease, ABLC was better tolerated, resulting in only very small changes in kidney function tests.

More recently studies have shown that exposure to azole treatment (including fluconazole, ketoconazole and itraconazole) results in the decreased antifungal activity of amphotericin B. This will likely be the case for newer, less toxic forms of the drug; but more studies are needed to confirm this. Like the quandary created by anti-HIV drug resistance, the development of antifungal resistance underlines the importance of developing new classes of drugs that can effectively treat candidiasis.

This article was provided by Project Inform. It is a part of the publication Project Inform Perspective.
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